"This is to officially, and under my hand, inform you fellow citizens of Zimbabwe and the world, that, with immediate effect, I no longer have anything to do with CCC" Chamisa said, in a statement.
"The original CCC idea has however been contaminated, bastardised, hijacked by ZANU PF through the abuse of State institutions," he said, accusing the ruling party of President Emmerson Mnangagwa of dirty tricks.
The surprise decision comes after Mnangagwa, 81, won a second term in office, beating the Citizens Coalition for Change (CCC) leader, in an election that also gave the ruling ZANU-PF party a majority in parliament.
International observers said the vote fell short of democratic standards and political tensions have since run high.
FILE - Zimbabwe's President Emmerson Mnangagwa delivers his speech during his inauguration ceremony at the National Sports Stadium in the capital Harare, Monday, Sept. 4, 2023.
Nicknamed "The Crocodile,he "first came to power after a coup that deposed veteran ruler Robert Mugabe in 2017.
Chamisa, 45, seemed to reference the nickname in his statement, declaring: "I will refuse to swim in a river with hungry crocodiles. We need to extricate ourselves from the shenanigans. I will have nothing to do with sewer pond politics."
Critics have long accused ZANU-PF of using the courts to target opposition politicians and silence dissent.
ZANU-PF secured 177 of the 280 national assembly seats with the CCC taking 104 after the August 23 poll.
Months later, more than 30 opposition lawmakers lost their seats under what analysts said appears to be an artificial political crisis.
In one event an obscure political figure declared himself the CCC's "interim secretary general" and said 14 MPs were no longer party members and could not keep their seats.
"The emergence of this imposter should not be looked at in isolation" from the election "sham," Chamisa said in Thursday's statement, "they are pursuing this agenda."
FILE - Supporters of Zimbabwe's main opposition leader Nelson Chamisa adresses are seen at a rally on the outskirts of Harare on July 26, 2023.
It is unclear what the leader, who claims CCC is now "hijacked" by ZANU-PF, plans to do next.
But he vowed to keep Zimbabweans "posted on the next step."
"CCC has now been rendered an extension of and been taken over by ZANU PF" he said.
"As a patriot, I remain active in public service" Chamisa said, "giving up or giving in is not an option."